Donnelly R, Bockman R S, Doty S B, Boskey A L
Department of Biochemistry, Hospital for Special Surgery, New York, NY 10021.
Bone Miner. 1991 Mar;12(3):167-79. doi: 10.1016/0169-6009(91)90030-4.
Gallium nitrate is a clinically effective agent for the treatment of cancer related hypercalcemia. The mechanism of action of this agent was investigated following development of a quantitative in vivo bone resorption assay modified from the method of Glowacki. In a preliminary study, the time course of resorption of 50 mg subcutaneous implants of bone powder in growing rats was followed by chemical analysis of mineral (ash and Ca) contents, enzymatic and histochemical assay of tartrate resistant acid phosphatase (TRAP) activity, and image analysis of changes in particle size using von Kossa stained sections. Day 21 was chosen as a single time point for the comparison of the extent of resorption of gallium-containing and control bone particles. Resorption of bone particles containing 0.39 micrograms Ga/mg bone was significantly inhibited relative to control particles. Mineral content (6.7 vs. 3.6 mg), Ca content (1.72 vs. 1.37 mg), and the percentage of the field covered by bone particles (12 vs. 9%) were greater in the animals which received gallium-containing bone particles. Similarly, the number of osteoclast-like cells and the TRAP activity in the gallium-containing bone particle implants at 21 days were increased relative to controls. These data indicate that gallium incorporation into bone matrix confers resistance to resorption.
硝酸镓是治疗癌症相关高钙血症的一种临床有效药物。在对Glowacki方法进行改良后建立了定量体内骨吸收试验，在此基础上对该药物的作用机制进行了研究。在一项初步研究中，通过对矿物质（灰分和钙）含量进行化学分析、对抗酒石酸酸性磷酸酶（TRAP）活性进行酶学和组织化学检测以及使用冯·科萨染色切片对颗粒大小变化进行图像分析，追踪了生长大鼠皮下植入50mg骨粉的吸收时间进程。选择第21天作为比较含镓骨颗粒和对照骨颗粒吸收程度的单一时间点。相对于对照颗粒，含0.39微克镓/毫克骨的骨颗粒的吸收受到显著抑制。接受含镓骨颗粒的动物的矿物质含量（6.7对3.6毫克）、钙含量（1.72对1.37毫克）以及骨颗粒覆盖区域的百分比（12对9%）更高。同样，相对于对照组，含镓骨颗粒植入物在21天时破骨细胞样细胞的数量和TRAP活性有所增加。这些数据表明，镓掺入骨基质可赋予骨抗吸收能力。
